Multiple Targets Improves PCR Clonality Testing in CLL

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Leukemia. 2006 Dec 14; [Epub ahead of print]

Significantly improved PCR-based clonality testing in B-cell

malignancies by use of multiple immunoglobulin gene targets. Report

of the BIOMED-2 Concerted Action BHM4-CT98-3936.

PA, Pott C, Groenen PJ, Salles G, Davi F, Berger F, JF,

van Krieken JH, Pals S, Kluin P, Schuuring E, Spaargaren M, Boone E,

D, ez B, Villuendas R, Gameiro P, Diss TC, Mills K,

GJ, GI, Milner BJ, Pearson D, Hummel M, Jung W, Ott M,

Canioni D, Beldjord K, Bastard C, Delfau-Larue MH, van Dongen JJ,

Molina TJ, Cabecadas J.

1Haematological Malignancy Diagnostic Service, The General Infirmary

at Leeds, Leeds, UK.

Polymerase chain reaction (PCR) assessment of clonal immunoglobulin

(Ig) and T-cell receptor (TCR) gene rearrangements is an important

diagnostic tool in mature B-cell neoplasms. However, lack of

standardized PCR protocols resulting in a high level of false

negativity has hampered comparability of data in previous clonality

studies.

In order to address these problems, 22 European laboratories

investigated the Ig/TCR rearrangement patterns as well as t(14;18)

and t(11;14) translocations of 369 B-cell malignancies belonging to

five WHO-defined entities using the standardized BIOMED-2 multiplex

PCR tubes accompanied by international pathology panel review. B-

cell clonality was detected by combined use of the IGH and IGK

multiplex PCR assays in all 260 definitive cases of B-cell chronic

lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal

zone lymphoma (n=41) and follicular lymphoma (n=109).

Two of 109 cases of diffuse large B-cell lymphoma showed no

detectable clonal marker. The use of these techniques to assign cell

lineage should be treated with caution as additional clonal TCR gene

rearrangements were frequently detected in all disease categories.

Our study indicates that the BIOMED-2 multiplex PCR assays provide a

powerful strategy for clonality assessment in B-cell malignancies

resulting in high Ig clonality detection rates particularly when IGH

and IGK strategies are combined.

Leukemia advance online publication, 14 December 2006;

doi:10.1038/sj.leu.2404479.

PMID: 17170731 [PubMed - as supplied by publisher]